WO2022189345A1

WO2022189345A1 - Flexible multilayer film having high low-temperature impact strength for medical packagings

Info

Publication number: WO2022189345A1
Application number: PCT/EP2022/055728
Authority: WO
Inventors: Susanne Holzer; René GROSS
Original assignee: Polycine Gmbh
Priority date: 2021-03-09
Filing date: 2022-03-07
Publication date: 2022-09-15
Also published as: JP2024509304A; CN117255746A; EP4304860A1

Abstract

Heat-sterilizable multilayer film having a high low-temperature impact strength comprising (a) a first polymer layer (A) containing polypropylene homopolymer modified with impact modifier; (b) a second polymer layer (B) containing: B1) 51% to 68% by weight of polypropylene terpolymer; B2) 12% to 22% by weight of styrene block copolymer elastomer; B3) 15% to 35% by weight of propylene-ethylene copolymer and (c) a middle polymer layer (C) containing: C1) 20% to 30% by weight of styrene block copolymer elastomer; C2) 15% to 30% by weight of polyethylene elastomer; C3) 40% to 65% by weight of propylene-ethylene copolymer; for use for medical packagings.

Description

Flexible multilayer film with high cold impact strength for medical packaging

The invention relates to heat-sterilizable multilayer films based on aliphatic polyolefins which have particularly good impact strength at relatively low temperatures, a process for their production and their use for medical packaging.

Multilayer films have been used for many years in a wide range of applications, e.g. in the food industry but also in the medical/pharmaceutical sector, for example as secondary packaging (outer packaging) or primary packaging for solution bags, dry concentrates and medication in tablet form.

Some multilayer films can be made into flexible packaging, which is useful, for example, as a pouch for packaging and dispensing medical solutions. As common practice, one currently finds medical solutions, e.g. B. infusion solutions for parenteral administration, in flexible disposable bags made of polyvinyl chloride (PVC) or non-PVC materials on the market.

In addition to the ability to collapse, which ensures that the bag completely leaks, these bags must also meet other performance criteria such as transparency, the ability to be sterilized with superheated steam at 121°C, sufficient mechanical strength, especially under dynamic loads in the weld seam area, good water vapor barrier, load capacity for standard pressure cuff applications, e.g. B. pressure infusions and from a pharmaceutical point of view have the least possible influence on the contents of the bag by the packaging. In accordance with the properties mentioned, multilayer films with a layered structure based on polyolefins have proven to be advantageous.

US Pat. No. 5,681,627 describes multilayer films - for medical applications such as medical bags - containing a) a first outer layer containing polyurethane (PU); b) a second outer layer (inner surface of a bag, sealing layer) preferably made of a blend of PP homo- or copolymer and elastomer; and c) a middle layer made of a polymeric adhesion promoter, preferably an ethylene/α-olefin copolymer. A blend of a propylene/ethylene copolymer (80%) and an SEBS block copolymer (20%) is preferably used as the second outer layer.

US Patent 5,695,840 describes 5-layer multilayer films - for medical applications such as medical bags - containing a) a first layer (inner surface of a bag, sealing layer) made of a blend of PP homo- or copolymer and elastomer; b) a second (middle) layer adjacent to a) of an ethylene/alpha-olefin copolymer; c) a third (middle) layer adjacent to b) (ethylene/alpha-olefin copolymer); d) a fourth adhesion-promoting layer adjacent to c) (anhydride-modified copolymers); and e) a fifth layer (outer layer) of a polyamide or copolyester.

US Patent 5,783,269 discloses heat sterilizable multilayer films for the manufacture of medical bags, comprising an outer layer (2), a backing layer (4) and a flexible middle layer (3) and optionally a heat seal layer (5), all layers being polyolefin homo- and/or copolymers (Softening point: (2) and (4) > 121 °C, (3) < 70 °C). Exemplary 4-layer films are made up of: (2) and (4) PP homopolymer, (3) PE or PP copolymer, (5) PP copolymer.

EP-A 0229475 describes a multi-layer film for medical containers, which is preferably 3-layer, containing (a) a first (= inner) heat-sealable layer made from a mixture of (i) polypropylene, (ii) an ethylene copolymer and (iii) a modifier such as another ethylene copolymer or an elastomer (e.g. EPDM terpolymer, SBS, SEBS, and SIS copolymer); (b) a second (middle) layer of a blend of (i) polyethylene (PE) (50 to 90% by weight) and (ii) a modifier; and (c) a third (outer) layer of a blend of (i) polypropylene and (ii) a modifier. Modified PP copolymers are preferably used for the outer layer.

EP-A 0199871 describes a flexible inter alia three-layer multilayer film for medical bags, comprising: (a) containing an (internal) sealing layer an (optionally modified) ethylene-propylene copolymer (ethylene content: 3.8% by weight); (b) a middle layer of a flexible polymeric material (eg an elastomeric co- or terpolymer such as EPDM); and (c) an outer layer containing an ethylene propylene copolymer.

DE-A 10361851 and WO 2020/127227 A1 describe a heat-sterilizable 3-layer multilayer film for the production of medical bags, the outer layer of which is made of polypropylene homopolymer modified with impact modifiers (at least 70% by weight, example 97% by weight), their The middle layer consists of polypropylene terpolymer modified with impact modifiers, and its (sealable) inner layer consists of polypropylene terpolymer and/or polypropylene copolymer modified with impact modifiers. Suitable impact modifiers are styrene-ethylene/butylene (SEBS), styrene-ethylene/propylene (SEPS) block copolymers or ethylene/α-olefin copolymers. The middle layer can contain 20 to 80% by weight of PP terpolymer, 0 to 40% by weight of polyethylene copolymer, 0 to 60% by weight of SEB or SEP block copolymer. Exemplary films have a middle layer made of 75% by weight PP terpolymer, 20% by weight SEBS block copolymer and 5% by weight PE plastomer (ethylene/octene copolymer), and an inner layer made of 85 or 75% by weight -% PP terpolymer, 15 or 20% by weight SEB block copolymer and 0 or 5% by weight PE plastomer.

DE 203 20 212 A1 describes a heat-sterilizable 3-layer multi-layer film produced by coextrusion for use in medical bags. Exemplary films have an outer layer of 97% by weight polypropylene homopolymer and 3% by weight SEBS block copolymer, a middle layer of 80% by weight EXCELLEN - a heterophasic copolymer based on polypropylene and polyethylene, and 20% by weight SEBS block copolymer, and an inner layer of 75% by weight PP terpolymer, 20% by weight SEBS block copolymer and 5% by weight PE plastomer.

Although good results in terms of flexibility, heat sterilizability and transparency have already been achieved with the known films, these films are particularly good in terms of impact strength, in particular lower temperatures, often 4 to -70° C., in particular -18 to -40° C., are still in need of improvement, and are only inadequately suitable for medical packaging that is stored in the refrigerator or freezer.

Materials available on the market for deep-freeze applications include packaging (e.g. bags) made from pure polyethylene (e.g. for food) or from polyvinyl chloride (e.g. for blood plasma). PE bags, which have very good low-temperature impact strength, have the disadvantage that they are not suitable for hot sterilization at 121 °C - as is required for medical films. Materials containing PVC are considered harmful to health as they commonly contain plasticizers which often escape, so attempts are being made to replace PVC with alternative materials. This applies all the more to medical packaging and to packaging that is stored in the refrigerator or freezer.

It is therefore an object of the invention to provide a heat-sterilizable multilayer film for medical packaging which requires particularly good low-temperature impact strength and which does not have the aforementioned disadvantages. Furthermore, the multi-layer film or packaging made from it should have properties such as high transparency, the ability to be sterilized with superheated steam at 121 °C, sufficient mechanical strength, especially under dynamic stress in the weld seam area, good water vapor barrier, load-bearing capacity for standard pressure cuff applications, e.g. pressure infusion, and the ability of bags to collapse maintained.

A further object of the invention is to provide a method for producing the heat-sterilizable multilayer film, in particular a method for producing a film tube based on the heat-sterilizable multilayer film.

One subject of the invention is a heat-sterilizable multilayer film comprising (consisting of) a) a first polymer layer (A) containing (consisting of) at least one, preferably one, polypropylene homopolymer modified with at least one, preferably one, impact modifier; b) a second polymer layer (B) containing (consisting of):

B1) 51 to 68% by weight - based on (B) - of at least one polypropylene

terpolymers;

B2) 12 to 22% by weight - based on (B) - at least one styrene

block copolymer (SBC) elastomers;

B3) 15 to 35% by weight - based on (B) - of at least one propylene-ethylene (block) copolymer in which - based on (B3) - the proportion of the structural units of ethylene is >9% by weight, often 9 up to 15% by weight, preferably >10% by weight; and c) a middle polymer layer (C) sandwiched between the first polymer layer

(A) and the second polymer layer (B), containing (consisting of): C1) 20 to 30% by weight - based on (C) - of at least one styrene

block copolymer (SBC) elastomers;

C2) 15 to 30% by weight - based on (C) - of at least one polyethylene

elastomer which is a copolymer of ethylene with an alpha-olefin containing from 4 to 12 carbon atoms;

C3) 40 to 65% by weight - based on (C) - of at least one propylene-ethylene

(Block)copolymers in which--based on (C3)--the proportion of structural units of ethylene is >9% by weight, often from 9 to 15% by weight, preferably >10% by weight.

The proportions given in percent by weight (% by weight) add up to 100% by weight in each case.

For the purposes of the present invention, the structural units of a monomer in a (co)polymer are to be understood as meaning the structural units derived from the polymerized monomer.

The term "heat-sterilizable" means that corresponding materials can be subjected to sterilization at elevated temperatures, preferably steam sterilization. Sterilization is a process by which the materials and objects are freed from living microorganisms. The state of the materials and objects thus achieved is referred to as “sterile”. In the steam sterilization of the filled or unfilled medical packaging, hot steam is used for sterilization, which is typically carried out in an autoclave. The medical packaging is preferably heated for 20 minutes to 121° C. at a pressure of 2 bar in steam. The air inside the autoclave is completely replaced by steam.

The term "multilayer film" refers to thermoplastic materials in multiple coextruded polymeric layers bonded together to form a film in the form of a continuous web or tube.

The term "impact modifier" refers to polymeric materials, such as styrenic block copolymer elastomers, polyethylene elastomers and polypropylene elastomers, which improve the impact strength of the polymer surrounding the impact modifier through incorporation in the melt state.

The term "impact strength" refers to the property of a material to withstand dynamic stress. According to the DIN EN ISO 180:2013-08 standard, the Izod impact strength of plastics can be measured under specified conditions.

First polymer layer (A)

By definition, the first polymer layer (A) of the multilayer film according to the invention represents the polymer layer which, when the film is processed into a package, which is preferably a bag, is on the outside of the package. Accordingly, when the film is further processed into packaging, it is in direct contact with the surface of the welding tool and therefore preferably requires a high melting or softening temperature, which is preferably above 125° C., particularly preferably between 127° C. and 150° C more preferably between 130°C and 145°C. The first polymer layer (A) contains at least one, preferably one, polypropylene homopolymer which is modified with at least one, preferably one, impact modifier.

The first polymer layer (A) preferably consists of at least one, preferably one, polypropylene homopolymer which is modified with at least one, preferably one, impact modifier.

Furthermore, the first polymer layer (A) preferably contains a polypropylene homopolymer which is modified with an impact modifier.

The first polymer layer (A) contains (or consists of) at least one, preferably one, polypropylene homopolymer which, in order to improve the (cold) impact strength, is generally 1 to 30% by weight, preferably 2 to 20% by weight, particularly preferably 2 to 10% by weight, in particular 3 to 5% by weight, of at least one impact modifier is modified.

The production of polypropylene homopolymers is known. Polypropylene homopolymers are also commercially available, for example from Lyondell Basell Corporation, USA.

The first polymer layer (A) preferably contains (or consists of) a polypropylene homopolymer which is mixed with at least one impact modifier selected from the group of styrene block copolymers, such as e.g. B. Styrene-ethylene-butylene-styrene block copolymers (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-isoprene-styrene block copolymer (SIS), and styrene-butadiene-styrene block copolymer (SBS) , preferably SEBS and SEPS, in particular SEBS, and/or from the group of copolymers of ethylene with at least one alpha-olefin containing 4 to 16, preferably 4 to 12, particularly preferably 4 to 8 carbon atoms, such as ethylene-butylene copolymers and /or ethylene-octene copolymers ethylene modified.

The first polymer layer (A) particularly preferably contains (or consists of) 90 to 98% by weight, in particular 95 to 97% by weight, of a polypropylene homopolymer and 2 to 10% by weight, in particular 3 to 5% by weight -%, of a styrenic block copolymer and/or a copolymer of ethylene with at least one alpha-olefin containing 4 to 12, preferably 4 to 8 carbon atoms. In a preferred embodiment, the first polymer layer (A) contains (or consists of) 95 to 97% by weight of a polypropylene homopolymer and 3 to 5% by weight of a styrene-ethylene/butylene block copolymer.

The weight data for the components of the first polymer layer (A) relate to the total weight of the first polymer layer (A).

Second polymer layer (B)

By definition, the second polymer layer (B) represents the polymer layer which, when the multilayer film according to the invention is processed into a package, which is preferably a bag, is on the inside of the package. This polymer layer is responsible for ensuring that the packaging can be sealed tightly by welding. The second polymer layer (B) of the film must be able to be welded to itself and to correspondingly inserted port elements safely and with the lowest possible temperature and welding time, and still be heat-sterilizable at temperatures of more than 121°C. A low welding temperature is particularly important in order to stress the film structure as little as possible with structural stresses. Accordingly, the melting or softening point of the second polymer layer (B) is generally above 121° C., preferably 122° C. to 135° C., particularly preferably 124° C. to 130° C., but in any case below the melting point - or softening point of the first polymer layer (A).

The second polymer layer (B) of the multilayer film according to the invention contains (or consists of) the components B1), B2) and B3) in the following proportions (in each case based on (B)):

B1) 51 to 68% by weight, preferably 55 to 67% by weight, particularly preferably 56 to 66%

wt%;

B2) 12 to 22% by weight, preferably 13 to 21% by weight, particularly preferably 14 to 20%

wt%;

B3) 15 to 35% by weight, preferably 17 to 32% by weight, particularly preferably 18 to 30%

wt%. Component B1)

Component B1) is at least one, preferably one, polypropylene terpolymer.

The term "terpolymer" denotes a copolymer made from three different monomers.

The term "polypropylene terpolymer" refers to a polypropylene molecular chain modified with two additional co-monomers in the polymerization process. Preferred additional comonomers are ethylene and/or at least one C4-C12a-olefin, preferably ethylene and a C4-C12a-olefin, particularly preferably ethylene and a C4-C8a-olefin, very particularly preferably ethylene and 1-butene.

Preference is given to B1) a terpolymer of propylene, ethylene and a C4-C12 α-olefin, in which the proportion of ethylene is preferably 1 to 4% by weight and the proportion of the C4-C12 α-olefin is preferably C4-C8 α-olefin , in particular 1-butene, preferably 9 to 12% by weight, based in each case on (B1).

The proportions by weight relate in each case to the polymerized structural units of the monomers in the terpolymer (B1).

The polypropylene terpolymer (component B1)) is very particularly preferably built up from structural units of propylene, ethylene and butylene.

The monomers are generally incorporated randomly in the polypropylene terpolymer (= component B1), i.e. polypropylene terpolymer B1) is usually a random polypropylene terpolymer.

The polypropylene terpolymer B1) is modified with components B2) and B3), which act as impact modifiers, to improve impact strength, particularly at low temperatures.

component B2)

Component B2) is at least one, preferably one, styrene block copolymer (SBC) elastomer. The term "styrene block copolymer elastomer" refers to synthetic thermoplastic elastomers based on styrene block copolymers for the impact modification of polypropylene.

The at least one styrene block copolymer (SBC) elastomer B2) is preferably selected from the group consisting of: styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene ethylene-propylene-styrene block copolymer (SEEPS), styrene-isoprene-styrene block copolymer (SIS) and styrene-butadiene-styrene block copolymer (SBS), and particularly preferably SEBS and SEPS, especially SEBS.

It is also possible to partially replace the styrene block copolymer (SBC) elastomer with one or more olefin-based thermoplastic elastomers (TPE-O) (TPE-O proportion: maximum 45% by weight, preferably 20 to 30% by weight) .

Component B2) is preferably a styrene block copolymer (SBC) elastomer which does not contain any fractions of an olefin-based thermoplastic elastomer.

component B3)

Component B3) is at least one, preferably one, propylene-ethylene (block) copolymer in which--based on (B3)--the proportion of the structural units of ethylene is >9% by weight, often from 9 to 15% by weight, preferably > 10% by weight, often preferably 10 to 12% by weight.

Propylene-ethylene copolymers B3) are often also referred to as “heterophasic” copolymers. In general, the propylene-ethylene copolymer B3) is a propylene-ethylene block copolymer which has ethylene and propylene polymer blocks and as a result forms a heterogeneous phase (morphology). Heterophasic propylene-ethylene (block) copolymers B3) differ both in their composition (fraction of ethylene structural units >9% by weight) and in their properties from propylene-ethylene copolymers--not used according to the invention as component B3). statistical distribution of the two monomers, in which the proportion of the structural units of ethylene is generally at most 8% by weight, is often a maximum of 5% by weight. Such random propylene-ethylene copolymers usually form a homogeneous phase (morphology).

Preferably contains (or consists of) the second polymer layer (B) according to the invention: a polypropylene terpolymer (component B1) composed of structural units of propylene, ethylene and butylene, a styrene-ethylene-butylene-styrene block copolymer (SEBS) (component B2), and a propylene-ethylene (block) copolymer (component B3).

The second polymer layer (B) according to the invention particularly preferably contains (or consists of):

B1) 55 to 67% by weight, preferably 56 to 66% by weight, of a polypropylene terpolymer built up from structural units of propylene, ethylene and butylene;

B2) 13 to 21% by weight, preferably 14 to 20% by weight, of a styrene-ethylene-butylene-styrene block copolymer (SEBS); and

B3) 17 to 32% by weight, preferably 18 to 30% by weight, of a propylene-ethylene (block) copolymer (component B3).

The weight data for the components B1), B2) and B3) of the second polymer layer (B) relate to the total weight of the second polymer layer (B).

Middle polymer layer (C)

The middle polymer layer (C) has the largest proportion by mass (at least 50% by weight) of the multilayer film, preferably 60 to 95% by weight, particularly preferably 70 to 90% by weight, very particularly preferably 75 to 85% by weight entire multilayer film and serves to improve the impact resistance of the entire structure.

The middle polymer layer (C) of the multilayer film according to the invention contains (or consists of) the components C1), C2) and C3) in the following proportions (in each case based on (C)):

C1) 20 to 30% by weight, preferably 21 to 30% by weight, particularly preferably 22 to 27%

wt%; C2) 15 to 30% by weight, preferably 15 to 25% by weight, particularly preferably 17 to 23%

wt%;

C3) 40 to 65% by weight, preferably 45 to 65% by weight, particularly preferably 50 to 60%

% by weight, most preferably 52 to 57% by weight.

Component C1)

Component C1) is at least one, preferably one, styrene block copolymer (SBC) elastomer.

Styrene block copolymer (SBC) elastomer C1) is defined like component B2), so that reference is made to the corresponding comments on component B2). component C2)

Component C2) is at least one, preferably one, polyethylene elastomer which is a copolymer of ethylene with an alpha-olefin containing 4 to 12, preferably 4 to 8 carbon atoms.

The proportion of the structural units of the alpha-olefin--based on (C2)--is preferably from 20 to 30% by weight.

The polyethylene elastomer C2) is particularly preferably an ethylene-butylene copolymer and/or an ethylene-1-octene copolymer, in particular an ethylene-1-octene copolymer.

component C3)

Component C3) is at least one, preferably one, propylene-ethylene (block) copolymer in which--based on (C3)--the proportion of the structural units of ethylene is >9% by weight, often from 9 to 15% by weight, preferably > 10% by weight, often preferably 10 to 12% by weight.

Propylene-ethylene (block) copolymer C3) is defined like component B3), so that reference is made to the corresponding comments on component B3).

According to the invention, the middle polymer layer (C) preferably contains (or consists of) a styrene-ethylene-butylene-styrene block copolymer (SEBS) (component C1)), an ethylene-1-octene copolymer (component C2)), and a propylene-ethylene (block) copolymer (component C3)). Particularly preferably contains (or consists of) the middle polymer layer (C) according to the invention

C1) 21 to 30% by weight, preferably 22 to 27% by weight, of a styrene-ethylene-butylene-styrene block copolymer (SEBS);

C2) 15 to 25% by weight, preferably 17 to 23% by weight, of an ethylene-octene copolymer; and

C3) 45 to 65% by weight, preferably 50 to 60% by weight, of a propylene-ethylene (block) copolymer (component C3)).

The weight data for components C1), C2) and C3) of the middle polymer layer (C) are based on the total weight of the middle polymer layer (C).

functional layer (D)

The heat-sterilizable multilayer film according to the invention can also comprise an additional functional layer D) as an outer layer, which is adjacent to the first polymer layer (A) on the outer side of (A) - i.e. on the other side of (A) opposite to the polymer layer (C) - located.

Functional layer (D) preferably has the effect that the heat-sterilizable multi-layer film and packaging made from it, such as medical bags or film tubes made from it, are gas-tight and/or watertight. Functional layer D) contains, preferably consists of, at least one, preferably one, material selected from the group consisting of: ethylene-vinyl alcohol copolymers, polyvinyl alcohols, polyamides, liquid-crystalline polymers (LCP), aromatic polyesters, preferably terephthalic acid polyesters, particularly preferably polyethylene terephthalates (PET), silicon oxide (SiO _x ), aluminum oxide (AIO _x ) and acrylate-based polymers.

The functional layer (D) preferably consists of PET/SiO _x .

The functional layer (D) preferably has a layer thickness of from 5 to 25 μm, in particular from 10 to 20 μm.

The gas barrier (for example the oxygen barrier) of the heat-sterilizable multilayer film according to the invention is provided by a functional layer (D) made of PET/SiO _x significantly improved, so that the film is also well suited for the storage of oxygen-sensitive ingredients.

With a SiOx/PET functional layer (D), the oxygen barrier (oxygen transmission rate (OTR)) of the heat-sterilizable multilayer film according to the invention can be increased by a factor of 1000 to OTR values <1 cm ³ /(m ² x day) ASTM F1927 (23 °C, 50% rH) can be reduced.

multilayer film

The heat-sterilizable multilayer film according to the invention preferably consists of the polymer layers (A), (B) and (C).

The multilayer film can contain in each of the polymer layers (A), (B) and (C) customary additives and/or processing aids which are suitable for the intended use of the multilayer film in customary amounts.

Preferred additives are antioxidants and thermal stabilizers (phosphitic and phenolic stabilizers such as Irgafos ^® 168, Irgafos P-EPQ, Irganox ^® 1076 or Irganox 1010), and acid scavengers such as DHT-4A ^® , synthetic hydrotalcite (SHT) and magnesium oxide (MgO).

The heat-sterilizable multilayer film made from the polymer layers (A), (B) and (C) according to the invention preferably contains at least one antioxidant, thermal stabilizer and/or acid scavenger, preferably in a total amount of <3000 ppm, based on the entire multilayer film .

The polymer layers (A), (B) and (C) preferably adhere to one another without using an adhesion promoter, ie the inventive multilayer film made from the polymer layers (A), (B) and (C) preferably contains no adhesion promoter. Furthermore, at least the second polymer layer (B) preferably contains no further additives and/or processing aids (e.g. modifiers or plasticizers such as mineral oil), very particularly preferably none of the polymer layers (A), (B) and (C) contain any other additives and /or processing aids, in addition to the additives mentioned above as preferred. Accordingly, there is no or hardly any Influencing of the drug or the medical solution held by the multilayer film according to the invention as packaging during sterilization and storage.

In the case of a multilayer film according to the invention consisting of the polymer layers (A), (B), (C) and the functional layer (D), the multilayer film generally contains an adhesion promoter or adhesive in addition to the additives mentioned above as preferred.

The layer thickness of the first polymer layer (A) is generally 5 to 15% by weight, preferably 7 to 13% by weight, particularly preferably 7.5 to 10% by weight, of the total film thickness of the multilayer film of the invention.

The layer thickness of the second polymer layer (B) is generally 5 to 15% by weight, preferably 7 to 13% by weight, particularly preferably 7.5 to 10% by weight, of the total film thickness of the multilayer film of the invention.

The middle polymer layer (C) makes up the largest proportion (preferably at least 70% by weight of the total film thickness) of the multilayer film according to the invention and serves to improve the impact strength of the entire structure.

In a multilayer film consisting of (A), (B) and (C), the layer thickness of the middle polymer layer (C) is generally from 70 to 85% by weight, preferably from 74 to 80% by weight.

If present, the layer thickness of the optional functional layer (D) is preferably 2.5 to 12.5% by weight, particularly preferably 5 to 10% by weight, of the total film thickness of the multilayer film of the invention.

The total film thickness (=thickness) of the multilayer film according to the invention is preferably 50 to 500 μm, particularly preferably 100 to 400 μm, very particularly preferably 150 to 300 μm. The overall film strength or thickness of a multilayer film according to the invention consisting of the polymer layers (A), (B) and (C) is preferably 50 to 500 gm, particularly preferably 100 to 400 gm, very particularly preferably 150 to 300 gm.

A multilayer film according to the invention which consists of the polymer layers (A), (B) and (C) and is characterized in that the total film thickness of the multilayer film is 50 to 500 gm, particularly preferably 100 to 400 gm, is particularly preferred, and - in each case based on the total film thickness of the multilayer film - the layer thickness of the first polymer layer (A) 5 to 15% by weight, preferably 7 to 13% by weight, the layer thickness of the second polymer layer (B) 5 to 15% by weight , preferably 7 to 13% by weight; and the layer thickness of the middle polymer layer (C) 70 to 85% by weight, preferably 74 to 80% by weight; amounts to; and the proportions of (A), (B) and (C) each add up to 100% by weight.

Process for producing the multilayer film

A further object of the invention is a process for producing the multilayer film according to the invention, the first polymer layer (A), the middle polymer layer (C) and the second polymer layer (B) being coextruded.

In the case of coextrusion, the plastic melts of the polymer layers (A), (B) and (C) are brought together before leaving the profile die of an extruder to form the multilayer film according to the invention.

The extrusion process is often two-stage. In a first step, the materials used for the individual polymer layers are mixed and compacted in extruders, preferably parallel twin-screw extruders (compounders), Fleiz cooling mixers or pellet presses. The plastic melts of the polymer layers (A), (B) and (C) are then brought together in another, directly coupled or spatially and temporally separate extruder before leaving the profile die to form the multilayer film according to the invention. The multilayer film obtained by the process according to the invention is preferably shock-cooled with water.

Through the coextrusion, the multilayer film according to the invention can be obtained in the form of a flat film (flat film process, e.g. when using a flat sheet die) or a film tube (blown film process, e.g. flooding the interior of the film tube with - preferably sterile filtered - air), with in the case of a film tube the Outside of the first polymer layer (A) and the inside of the second polymer layer (B).

In a further process step, the optional functional layer (D) can be applied to the multilayer film obtained by the process according to the invention--e.g. by hot lamination or preferably by lamination.

According to a particular embodiment for producing a laminated multilayer film tube according to the invention, the method according to the invention comprises the following steps:

(a') Production of a film tube from the multi-layer film according to the invention by a blown film process, the interior of the film tube being flooded with - preferably sterile filtered - air;

(b ¹ ) optionally cooling the tubular film produced in process step (a ¹ );

(c ¹ ) coating the optionally cooled tubular film with a pressure-sensitive adhesive layer on at least one side (first polymer layer (A)) of the tubular film;

(d ¹ ) optionally drying the tubular film provided with the pressure-sensitive adhesive layer;

(e ¹ ) laminating the at least one side of the tubular film coated with the pressure-sensitive adhesive layer (first polymer layer (A)) with a functional layer (D), in particular a SiOx/PET functional layer; (f) optionally drying or curing the laminated tubular film.

According to the method according to the invention of the aforementioned embodiment, the two parallel inner sides (= second polymer layer (B)) adhere of the tubular film after the melt or coextrusion of the tubular film, preferably directly one on top of the other, so that a coating of the outer sides (first polymer layers (A)) of the tubular film is possible with a closed interior of the tubular film. The closed interior space, which is inflated when the resulting tubular film is later used, is therefore essentially particle-free.

In the method according to the invention of the aforementioned embodiment, the interior of the tubular film is preferably flooded with sterile-filtered air, so that a low-particle, laminated multi-layer tubular film is obtained which is particularly well suited for medical purposes.

In order to produce a low-particle, laminated multi-layer film tube, the aforementioned method according to the invention is particularly preferably carried out in a clean room.

In the method according to the invention according to the above embodiment, preference is given to using an adhesion promoter which enables complete curing at room temperature after approximately 2 weeks, preferably 1 week. In a heating chamber, curing can also take place more quickly at an elevated temperature, preferably 30° C. or more, often 40° C. to 60° C.

Suitable adhesion promoters (contact adhesives, adhesive adhesives or laminating adhesives) are, for example, isocyanates, polyurethanes, poly(ethyl acrylate/methacrylic ester), pure acrylate copolymers, vinyl ester/acrylate copolymers or inorganic-organic hybrid polymers.

Preferred adhesion promoters are two-component systems, which may or may not contain solvents, and may contain or contain silane or be silane-free and may optionally be used with an additional “catalyst” to accelerate curing.

Suitable solvent-based two-component systems are, for example, polyurethane adhesives, including commercially available systems such as - Dow ADCOTE™ 675A + ADCOTE™ 675C coreactant;

- Dow ADCOTE 811 A + ADCOTE 811 B coreactant;

- Dow ADCOTE E735A-75 + ADCOTE™ E735C2 coreactant:

- MORCHEM PS 241 AE + CS-97 coreactant,

- Henkel Loctite Liofol LA2798 + Henkel Loctite Liofol LA7371 ;

- Henkel LOCTITE HY 4070 2K hybrid adhesive.

The foregoing systems can optionally be used with "Catalysts" including such as Dow Catalyst 9L10 (polyisocyanate), Dow Catalyst 9L200 and Dow Catalyst F Adcote 40-3E which are commercially available.

Suitable solvent-free two-component systems are, for example, polyurethane adhesives and other commercially available systems such as

- Dow MOR-FREE™ L 75-720 Adhesive

+ CR 88-720 or CR 88-721 or MOR-FREE™ C 79 S coreactant

- Dow MOR-FREE™ 203A Adhesive + MOR-FREE™ 200C coreactant

- Dow MOR-FREE™ L705 Adhesive + MOR-FREE™ C 79 or MOR-FREE™ C-102 coreactant.

Alternatively, one-component systems can also be used as adhesion promoters, which can contain or be solvent-free and contain or contain silane and can optionally be used with an additional “catalyst” to accelerate curing.

Suitable solvent-free one-component systems are, for example, Dow MOR-FREE™ ELM 415A (polyurethane adhesive) or SENOBOND®-WB FOIL LAMINATION ADHESIVE FP NDC 375224, which are commercially available.

The adhesive is particularly preferably selected in such a way that it meets the requirements of pharmacopeia limits, for example with regard to migration properties, and is preferably free from organic solvents.

Depending on the procedure or the desired coating, the adhesive layer can be applied to one or both sides of the tubular film produced by coextrusion. This can for example by spraying or doctoring done. The use of aqueous solutions of the corresponding adhesives is also suitable.

After these adhesive layers have been applied, the resulting film tube can optionally be dried. For example, when the adhesive is applied using water, drying can be done by evaporating the water. The layer thicknesses of the pressure-sensitive adhesive layers are preferably in the range from 1 to 10 μm.

The subject of the invention is also the use of the multilayer film according to the invention for producing a medical packaging, preferably a medical bag.

The invention also relates to the use of the medical packaging according to the invention as a container for at least one medicament.

The medical packaging according to the invention is particularly suitable as a container for at least one medicament, the multilayer film according to the invention being particularly suitable for the packaging and storage of medical solutions at sub-zero temperatures due to the specially modified polymer layer (C).

In a preferred embodiment, the packaging according to the invention is divided into chambers, so that it can be used as a container for several medicaments at the same time. This is relevant, for example, for drug combinations that have to be administered together but are not stable in combination over long periods of time, or for solid drugs that are administered in the form of a solution or suspension but not over in the solution or suspension are stable for longer periods. Separate chambers allow the components of the final administration form to be stored separately and mixed with one another just before administration by opening the separation points.

A method for producing a medical packaging according to the invention, preferably a bag, comprises the steps: a) providing at least one heat-sterilizable multilayer film according to the invention; b) optionally providing one or more port elements and/or hoses; c) Forming a medical package, preferably a bag, from the at least one heat-sterilizable multilayer film, so that the second polymer layer (B) is the inner surface of the medical package, preferably the bag, and the first polymer layer (A) is the outer surface of the medical package , preferably the pouch; d) optionally positioning the port elements and/or tubes between the inner surfaces on the contours of the medical packaging, preferably the bag; e) bringing the inner surfaces on the contours of the medical packaging, preferably the bag, into contact with one another and with port elements and/or tubes optionally positioned in between; f) Welding the inner surfaces on the contours of the medical packaging, preferably the bag, to one another and with port elements and/or tubes optionally positioned in between.

In step a), the multilayer film according to the invention is preferably provided in the form of a flat film or a tubular film. Depending on the form of foil provided, the further procedure may differ in certain details. The resulting low-particle film tube can be laminated with a functional layer (D), e.g. a SiOx/PET functional layer, using additional process steps.

Depending on the application of the medical packaging according to the invention, preferably the bag, additional elements such as port elements and/or hoses can optionally be provided in step b) in the method after the provision of the multilayer film according to the invention. The provision of these elements makes sense, for example, if the medical packaging according to the invention, preferably the bag, is to be used as a fixed component of a medical device or is to be connected to a medical device. The omission of the step b) can be useful, for example, if the medical packaging, preferably the bag, is only used to store a medicament and is damaged in order to remove the medicament, for example by tearing it open or piercing it with a cannula.

In step c), the multilayer film provided according to the invention is brought into the form of medical packaging, preferably a pouch. If a tubular film was provided in step a), the shaping of the medical packaging, preferably the bag, can only include cutting the tubular film to the desired length, for example, since the second polymer layer (B) already contains the inner surface of the tubular film and the first polymer layer (A) forms the outer surface of the tubular film. If a flat film was provided in step a), the medical packaging, preferably the bag, can be formed in step c), for example from a piece of multilayer film, by cutting this piece into a mirror-symmetrical shape and folding it over along the mirror axis so that the edges of the film are laid congruently on top of each other, with the second polymer layer (B) on the inside. Alternatively, the medical packaging according to the invention, preferably the bag, can be formed from two pieces of flat film, for example, by cutting the two pieces mirror-symmetrically to one another and placing them congruently on top of one another, with the second polymer layer (B) on the inside. When cutting to size, rectangular shapes are particularly preferred, as this results in the least loss of material and is easiest to process. However, other shapes are also possible, so that, for example, medical packaging, preferably a pouch, can be produced with an aesthetic shape that is appealing to children and distracts them from the actual administration of a medicament.

Depending on whether additional elements such as port elements and/or tubing were provided in step b), these elements can be positioned in step d) between the inner surfaces at the contours of the formed medical package, preferably the pouch. In the case of a tubular film, this means inserting the additional elements into the openings of the tubular film. In this case, the elements can only be placed on two opposite ones Sides of the medical packaging, preferably the pouch, are positioned. In the case of a flat film, what is meant is the insertion of the additional elements between the edges of the one or more pieces of flat film laid congruently on top of one another in step c). The elements can be positioned anywhere along the edges, preferably at most on two opposite edges.

In step e), the inner surfaces of the shaped medical packaging, preferably the bag, are brought into contact at their contours with one another and with the additional elements that may be located between the inner surfaces, so that these can be brought into contact in step f) by supplying strands and mechanical pressure, if necessary can be welded together. During the welding, the temperature is preferably selected such that it is above the melting or softening point of the second polymer layer (B), but below the melting or softening point of the first polymer layer (A). Fliering can ensure that the second polymer layer (B) melts on the contours of the medical packaging, preferably the bag, and thereby closes it tightly and fluid-tight, while the first polymer layer (A) retains its shape and thereby the stability of the medical packaging, preferably of the bag.

An important criterion for the use of the multilayer film according to the invention as primary packaging for medical solutions is the barrier effect against loss of liquid. Such a loss of liquid results in a concentration of the active substances in the solution, which must not exceed certain values. The loss of liquid during storage determines, among other things, the shelf life of the product. The formulation of the multilayer film according to the invention is chosen such that a very good water vapor barrier is achieved with good impact strength.

The heat-sterilizable multilayer film according to the invention is characterized in that it can also be reliably welded to port elements using a thermally permanently heated welding process, does not require plasticizers, has little effect on medical solutions and has a high water vapor barrier. Simultaneously the multilayer film according to the invention has a significantly improved low-temperature impact strength even at sub-zero temperatures. Multilayer films according to the invention provided with an additional functional layer (D), in particular a SiOx/PET functional layer, have a significantly improved gas barrier, which also allows storage of oxygen-sensitive ingredients.

The invention is explained in more detail below using examples, without restricting it as a result.

Example 1 :

First polymer layer (A):

- 97% by weight of ^Moplen® HP525J from Lyondell Basell Corp., USA/ Polypropylene homo-polymer

- 3 wt% ^Tuftec® H1062 from Asahi Kasei, Japan/styrene-ethylene/butylene block copolymer

The formulation mentioned was mixed in the melt state in a separate compounding step and granulated for further use.

Second polymer layer (B):

- 65 wt% Bormed ^® TD109CF from Borealis, Austria/ polypropylene terpolymer

- 15% by weight of ^Tuftec® H1062 from Asahi Kasei, Japan/styrene-ethylene/butylene block copolymer

- 20 wt% Bormed ^® SC 820 CF-11 from Borealis, Austria/heterophasic propylene copolymer

Middle polymer layer (C):

- 55% by weight Bormed ^® SC 820 CF-11 from Borealis, Austria/heterophasic propylene copolymer - 25% by weight of ^Tuftec® H1062 from Asahi Kasei, Japan/ styrene-ethylene/butylene block copolymer

- 20% by weight Engage ^® 8003 from Dow Chemical Company, USA/ ethylene octene polyolefin elastomer

The melts from the granulated compounds of the first polymer layer (A), the middle polymer layer (C) and the second polymer layer (B) were coextruded with the usual process parameters for polypropylene (temperature 180 to 230°C) on a blown film line with water cooling and a multilayer film in the form of a film tube whose interior was flooded with sterile filtered air was obtained.

The film was produced with a total thickness of 200 μm, the first polymer layer (A) and second polymer layer (B) each having a thickness of 15 μm and the middle polymer layer (C) having a thickness of 170 μm.

The film produced can be sterilized with superheated steam and firmly welded with welding tools at a temperature of 125°C.

Example 2:

A tubular film produced according to Example 1 was additionally provided on both sides with a functional layer (D) of SiOx/PET (Techbarrier™ from Mitsubishi) with a layer thickness of 15 μm in each case.

First, a two-component adhesive (Dow ADCOTE 811A + ADCOTE 811 B coreactant, as well as Dow Catalyst 9L10, available from Dow Chemical) was applied to both sides of the flattened film tube and then the film tube provided with the adhesive was laminated on both sides with the functional layer.

The foil produced can be sterilized with superheated steam and can already be firmly welded with welding tools at a temperature of 125°C. Example 3 (not according to the invention):

First polymer layer (A):

- 97% by weight of Moplen ^® HP525J from Lyondel IBasell Corp., USA/ Polypropylene homopolymer

Second polymer layer (B):

- 70% by weight Bormed ^® TD109CF from Borealis, Austria/ polypropylene terpolymer

- 15% by weight of ^Tuftec® H1062 from Asahi Kasei, Japan/ styrene-ethylene/butylene block copolymer

- 15 wt% Bormed ^® RD804 CF-11 , Borealis, Austria/propylene random copolymer

Middle polymer layer (C):

- 55 wt% Bormed ^® TD109CF from Borealis, Austria/ polypropylene terpolymer

- 10% by weight Bormed ^® SC 820 CF-11 from Borealis, Austria/heterophasic propylene copolymer

- 20% by weight of ^Tuftec® H1062 from Asahi Kasei, Japan/ styrene-ethylene/butylene block copolymer

- 15% by weight Engage ^® 8003 from Dow Chemical Company, USA/ ethylene octene polyolefin elastomer

The melts from the granulated compounds of the first polymer layer (A), the middle polymer layer (C) and the second polymer layer (B) were with for Polypropylene usual process parameters (temperature 180 to 230 ° C) coextruded on a blown film line with water cooling and a multi-layer film in the form of a film tube whose interior was flooded with sterile filtered air was obtained.

The film was produced with a total thickness of 200 μm, the first polymer layer (A) and second polymer layer (B) each having a thickness of 15 μm and the middle polymer layer (C) having a thickness of 170 μm. The film produced can be sterilized with superheated steam and can be firmly welded using welding tools at a temperature of 125°C.

Example 4 (comparative example (according to DE 10361851 A1, example 1)):

First polymer layer (A):

- 97% by weight ^Moplen® HP525J from LyondellBasell Corp., USA/ Polypropylene homo-polymer

Second polymer layer (B):

- 85 wt% Bormed ^® TD109CF from Borealis, Austria/ polypropylene terpolymer

Middle polymer layer (C): - 75 wt% Bormed ^® TD109CF from Borealis, Austria/ polypropylene terpolymer

- 5% by weight Engage ^® 8003, Dow Chemical Company, USA/ ethylene octene polyolefin elastomer

The film was coextruded on a water-cooled blown film line using the usual process parameters for polypropylene.

To check the impact strength of the films obtained, a drop test according to DIN EN ISO 15747:2019-07 is carried out.

Description:

- preparation of infusion (IV) bags of desired size, e.g., 1000ml;

- IV bags are filled with e.g. water and tightly closed (e.g. stopper);

- IV bags are superheated steam sterilized at 121°C and must cool down completely;

- 10 sachets are stored at 20°C, at 4°C and at -18°C for 24 hours each;

- Then the bags from the corresponding fleas (DIN EN ISO 15747:2019-07, Table A.1) are dropped on the floor. A 1000ml bag is placed on a 0.75m flea (device) and then dropped onto the floor.

The test results for a bag with a capacity of 1000 ml (contents: water) are shown in Table 1.

Failure rate ^* : defective bags / number of bags tested

The results of the drop test show a direct correlation between the weight percentage of the impact modifier in the middle layer and the low-temperature impact strength at minus temperatures. Only the multilayer films of Examples 1 and 2 pass the drop test at temperatures of 4°C and -18°C due to the composition according to the invention (specific impact modifiers in all layers (A), (B) and (C) in specific amounts).

Claims

patent claims

1. Heat-sterilizable multilayer film, comprising a) a first polymer layer (A) containing at least one polypropylene homopolymer modified with at least one impact modifier; b) a second polymer layer (B) containing:

B1) 51 to 68% by weight - based on (B) - of at least one

polypropylene terpolymers;

B2) 12 to 22% by weight - based on (B) - of at least one styrene

block copolymer (SBC) elastomers;

B3) 15 to 35% by weight - based on (B) - of at least one propylene

Ethylene (block) copolymers in which - based on (B3) - the proportion of structural units of ethylene is >9% by weight, often from 9 to 15% by weight; and c) a middle polymer layer (C) located between the first polymer layer (A) and the second polymer layer (B) containing:

C1) 20 to 30% by weight - based on (C) - of at least one styrene

block copolymer (SBC) elastomers;

C2) 15 to 30% by weight - based on (C) - of at least one

polyethylene elastomer which is a copolymer of ethylene with an alpha-olefin containing 4 to 12 carbon atoms;

C3) 40 to 65% by weight - based on (C) - of at least one propylene

Ethylene (block) copolymers in which - based on (C3) - the proportion of structural units of ethylene is >9% by weight, often from 9 to 15% by weight.

2. Heat sterilizable multilayer film according to claim 1, wherein the second polymer layer (B) contains:

B1) 55 to 67% by weight, preferably 56 to 66% by weight;

B2) 13 to 21% by weight, preferably 14 to 20% by weight;

B3) 17 to 32% by weight, preferably 18 to 30% by weight.

3. Heat-sterilizable multilayer film according to claim 1 or 2, wherein component B1) is a terpolymer of propylene, ethylene and a C4-C12 C1-olefin, preferably a terpolymer of propylene, ethylene and butylene.

4. Heat-sterilizable multilayer film according to any one of claims 1 to 3, wherein the styrene block copolymer (SBC) elastomer B2) and/or C1) is selected from the group consisting of: styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene -ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-ethylene-propylene-styrene block copolymer ( SEEPS ), styrene-isoprene-styrene-

block copolymer (SIS) and styrene-butadiene-styrene block copolymer (SBS), and particularly preferably SEBS and SEPS, especially SEBS.

5. Heat sterilizable multilayer film according to any one of claims 1 to 4, wherein the middle polymer layer (C) contains:

C1) 21 to 30% by weight, preferably 22 to 27% by weight;

C2) 15 to 25% by weight, preferably 17 to 23% by weight;

C3) 45 to 65% by weight, preferably 50 to 60% by weight.

6. The heat-sterilizable multilayer film as claimed in any of claims 1 to 5, in which the polyethylene elastomer C2) is an ethylene-butylene copolymer and/or an ethylene-octene copolymer, in particular an ethylene-octene copolymer.

7. The heat-sterilizable multilayer film as claimed in any of claims 1 to 6, in which the propylene-ethylene copolymer B3) and/or C3) is a propylene-ethylene block copolymer.

8. Heat-sterilizable multilayer film according to any one of claims 1 to 7, wherein the first polymer layer (A) contains 90 to 98% by weight, in particular 95 to 97% by weight, of a polypropylene homopolymer and 2 to 10% by weight, in particular 3 to 5% by weight of at least one, preferably one, impact modifier selected from styrene block copolymers and/or copolymers of ethylene with at least one alpha-olefin containing 4 to 12, preferably 4 to 8 carbon atoms.

9. Heat-sterilizable multilayer film according to any one of claims 1 to 8, characterized in that the multilayer film consists of the polymer layers (A), (B) and (C), and the total film thickness of the multilayer film is 50 to 500 μm, preferably 100 to 400 μm , is, and - in each case based on the total film thickness of the multilayer film - the layer thickness of the first polymer layer (A) is 5 to 15% by weight, preferably 7 to 13% by weight, the layer thickness of the second polymer layer (B) is 5 to 15 wt%, preferably 7 to 13 wt%; and the layer thickness of the middle polymer layer (C) 70 to 85% by weight, preferably 74 to 80% by weight; amounts to.

10. A process for producing a multilayer film according to any one of claims 1 to 9, wherein the first polymer layer (A), the middle polymer layer (C), and the second polymer layer (B) are coextruded.

11. Heat sterilizable multilayer film according to any one of claims 1 to 9, which comprises an additional functional layer (D) which is located adjacent to the first polymer layer (A) on the outer side of (A), and wherein functional layer (D ) contains at least one material selected from the group consisting of: ethylene-vinyl alcohol copolymers, polyvinyl alcohols, polyamides, liquid-crystalline polymers (LCP), aromatic polyesters, preferably terephthalic acid polyesters, particularly preferably

polyethylene terephthalates (PET), silicon oxide (SiO _x ), aluminum oxide (AlO _x ) and acrylate-based polymers.

12. Heat sterilizable multilayer film according to claim 11, wherein

Functional layer (D) consists of PET/SiO _x .

13. A method for producing a laminated multi-layer film tube from a multi-layer film according to claim 11 or 12, comprising the following steps:

(a') Fierstellen a film tube from a multi-layer film produced according to claim 10 by a blown film process, wherein the Interior of the film tube with - is flooded air - preferably sterile filtered;

(b ¹ ) optionally cooling the tubular film produced in process step (a ¹ );

14. Use of a multilayer film according to any one of claims 1 to 9, 11 or 12 for the production of medical packaging, preferably a medical bag.

15. A method for producing medical packaging, preferably a bag, from a multilayer film according to claims 1 to 9, 11 or 12, comprising the steps of: a) providing at least one multilayer film produced according to claim 10 or 13; b) optionally providing one or more port elements and/or hoses; c) Forming a medical package, preferably a bag, from the at least one multilayer film, so that the second polymer layer (B) is the inner surface of the medical package, preferably the bag, and the first polymer layer (A) is the outer surface of the medical package, preferably the pouch; d) optionally positioning the port elements and/or tubes between the inner surfaces on the contours of the medical packaging, preferably the bag; e) bringing the inner surfaces on the contours of the medical packaging, preferably the bag, into contact with one another and with port elements and/or tubes optionally positioned in between; f) Welding the inner surfaces on the contours of the medical packaging, preferably the bag, to one another and with port elements and/or tubes optionally positioned in between.